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Nyberg L.,Umeå University | Nyberg L.,Umea Center for Functional Brain Imaging | Salami A.,Umeå University | Salami A.,Umea Center for Functional Brain Imaging | And 15 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.


Lovden M.,Karolinska Institutet | Lovden M.,Max Planck Institute for Human Development | Kohncke Y.,Karolinska Institutet | Laukka E.J.,Karolinska Institutet | And 7 more authors.
NeuroImage | Year: 2014

The integrity of the brain's white matter is important for neural processing and displays age-related differences, but the contribution of changes in white matter to cognitive aging is unclear. We used latent change modeling to investigate this issue in a sample of very old adults (aged 81-103. years) assessed twice with a retest interval of 2.3. years. Using diffusion-tensor imaging, we probed white matter microstructure by quantifying mean fractional anisotropy and mean diffusivity of six major white matter tracts. Measures of perceptual speed, episodic memory, letter fluency, category fluency, and semantic memory were collected. Across time, alterations of white matter microstructure in the corticospinal tract were associated with decreases of perceptual speed. This association remained significant after statistically controlling for changes in white matter microstructure in the entire brain, in the other demarcated tracts, and in the other cognitive abilities. Changes in brain volume also did not account for the association. We conclude that white matter microstructure is a potent correlate of changes in sensorimotor aspects of behavior in very old age, but that it is unclear whether its impact extends to higher-order cognition. © 2014 Elsevier Inc.


Kompus K.,Umea Center for Functional Brain Imaging | Kompus K.,Umeå University | Kompus K.,University of Bergen | Kalpouzos G.,Umea Center for Functional Brain Imaging | And 3 more authors.
Brain Research | Year: 2011

Functional lateralization of episodic memory processes in the frontal lobe is an area of intense study in the field of cognitive neuroimaging. Yet, to date there is insufficient knowledge of what role the interhemispheric structural connectivity plays in this lateralized organization. We analyzed functional and structural magnetic resonance imaging data from healthy adult volunteers who performed an associative encoding and retrieval task. We examined the relationship between functional voxel-based relative asymmetry of encoding and retrieval in the frontal lobes and the size of the anterior corpus callosum (antCC; corrected for brain size). The size of the antCC was strongly associated to the relative encoding-retrieval asymmetry in the ventrolateral prefrontal cortex (BA 47). These findings show that the functional asymmetry of episodic memory processes in the frontal lobes is associated with the structural connectivity between the hemispheres. © 2011 Elsevier B.V. All rights reserved.


Kalpouzos G.,Umeå University | Kalpouzos G.,Umea Center for Functional Brain Imaging | Kalpouzos G.,Karolinska Institutet | Persson J.,University of Stockholm | And 2 more authors.
Neurobiology of Aging | Year: 2012

Functional brain imaging studies of normal aging typically show age-related under- and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under- and overrecruitment was accounted for by GMv changes. Occipital GMv loss accounted for underrecruitment at encoding. Efficiency reduction of sensory-perceptual mechanisms underpinned by these areas may partly be due to local atrophy. At retrieval, local GMv loss accounted for age-related overactivation of left dorsolateral prefrontal cortex, but not of left dorsomedial prefrontal cortex. Local atrophy also accounted for age-related overactivation in left lateral parietal cortex. Activity in these frontoparietal regions correlated with performance in the older group. Atrophy in the overrecruited regions was modest in comparison with other regions as shown by a between-group voxel-based morphometry comparison. Collectively, these findings link age-related structural differences to age-related functional under- as well as overrecruitment. © 2012 Elsevier Inc.


Salami A.,Umea Center for Functional Brain Imaging | Salami A.,Umeå University | Salami A.,Karolinska Institutet | Pudas S.,Umea Center for Functional Brain Imaging | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alterations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN-HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25-80 y old), we have demonstrated agerelated decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which agerelated elevation of connectivity between left and right HC was found along with attenuated HC-cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural recruitment and HC-cortical connectivity during activememory encoding, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico-hippocampal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing.


Josefsson M.,Umeå University | Josefsson M.,Umea Center for Functional Brain Imaging | De Luna X.,Umeå University | Pudas S.,Umea Center for Functional Brain Imaging | And 6 more authors.
Journal of the American Geriatrics Society | Year: 2012

Objectives To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health-related, and genetic predictors of stability or decline. Design Prospective cohort study. Setting The Betula Project, Umeå, Sweden. Participants One thousand nine hundred fifty-four healthy participants aged 35 to 85 at baseline. Measurements Memory was assessed according to validated episodic memory tasks in participants from a large population-based sample. Data were analyzed using a random-effects pattern-mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory. Results Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age-typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol-O-methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E É 4 allele was more frequent in decliners. Conclusion Quantitative, attrition-corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.


Salami A.,Umea Center for Functional Brain Imaging | Salami A.,Umeå University | Eriksson J.,Umea Center for Functional Brain Imaging | Eriksson J.,Umeå University | And 7 more authors.
NeuroImage | Year: 2010

Previous studies have shown that information that currently cannot be retrieved but will be retrieved on a subsequent, more supported task (i.e. is available but not accessible) has a distinct neural signature compared with non-available information. For verbal paired-associates, an availability signal has been revealed in left middle temporal cortex, an area potentially involved in the storage of such information, raising the possibility that availability signals are expressed in modality-specific storage sites. In the present study subjects encoded pictures and sounds representing concrete objects. One day later, during fMRI scanning, a verbal cued-recall task was administrated followed by a post-scan recognition task. Items remembered on both tasks were classified as accessible; items not remembered on the first but on the second task were classified as available; and items not remembered on any of the tasks were classified as not available. Multivariate partial-least-squares analyses revealed a modality-independent accessibility network with dominant contributions of left inferior parietal cortex, left inferior frontal cortex, and left hippocampus. Additionally, a modality-specific availability network was identified which included increased activity in visual regions for available pictorial information and in auditory regions for available sound information. These findings show that availability in memory, at least in part, is characterized by systematic changes in brain activity in sensory regions whereas memory access reflects differential activity in a modality-independent, conceptual network, thus indicating qualitative differences between availability and accessibility in memory. © 2010 Elsevier Inc.


Salami A.,Umea Center for Functional Brain Imaging | Salami A.,Umeå University | Eriksson J.,Umea Center for Functional Brain Imaging | Eriksson J.,Umeå University | And 3 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2012

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n. = 287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. © 2011 Elsevier B.V.


Persson J.,University of Stockholm | Persson J.,Umea Center for Functional Brain Imaging | Pudas S.,University of Stockholm | Pudas S.,Umea Center for Functional Brain Imaging | And 3 more authors.
Neurobiology of Aging | Year: 2014

Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49-79years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging. © 2014 Elsevier Inc.


Kalpouzos G.,Umeå University | Kalpouzos G.,Umea Center for Functional Brain Imaging | Eriksson J.,Umeå University | Eriksson J.,Umea Center for Functional Brain Imaging | And 4 more authors.
PLoS ONE | Year: 2010

Background: Prospective memory (PM) denotes the ability to remember to perform actions in the future. It has been argued that standard laboratory paradigms fail to capture core aspects of PM. Methodology/Principal Findings: We combined functional MRI, virtual reality, eye-tracking and verbal reports to explore the dynamic allocation of neurocognitive processes during a naturalistic PM task where individuals performed errands in a realistic model of their residential town. Based on eye movement data and verbal reports, we modeled PM as an iterative loop of five sustained and transient phases: intention maintenance before target detection (TD), TD, intention maintenance after TD, action, and switching, the latter representing the activation of a new intention in mind. The fMRI analyses revealed continuous engagement of a top-down fronto-parietal network throughout the entire task, likely subserving goal maintenance in mind. In addition, a shift was observed from a perceptual (occipital) system while searching for places to go, to a mnemonic (temporo-parietal, fronto-hippocampal) system for remembering what actions to perform after TD. Updating of the top-down fronto-parietal network occurred at both TD and switching, the latter likely also being characterized by frontopolar activity. Conclusion/Significance: Taken together, these findings show how brain systems complementary interact during realworld PM, and support a more complete model of PM that can be applied to naturalistic PM tasks and that we named PROspective MEmory DYnamic (PROMEDY) model because of its dynamics on both multi-phase iteration and the interactions of distinct neurocognitive networks. © 2010 Kalpouzos et al.

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